It is the intention of this work to examine the phenomenon of programming (imprinting) steroid metabolizing enzymes in the rat in an effort to determine the role of the endocrine system in this process. Initial studies examine the ontogenesis of selected steroid metabolizing enzymes (i.e., 5 alpha-reductase and 16 alpha-hydroxylase), noting in particular the programmed divergence in these enzymes activities in the male and female after puberty. Studies will then be performed to determine whether exposure to various hormonally-active xenobiotics can alter the normal process of hepatic and gonadal enzyme programming. The critical period of development will be determined by exposing animals to the xenobiotics either prenatally or postnatally. Particular attention will be given to the enzyme 5-alpha-reductase, which has a dual localization, i.e. in the endoplasmic reticulum and the nucleus. The programming studies on this enzyme are conducted in both subcellular fractions to determine if enzyme localization alters the sensitivity to the programming process. The hormonally-active agents of interest include DES, various PCB isomers, zearanol, and the normal endogenous steroids.